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Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 52867

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Special Issue Editors

Prof. Dr. Vladimir Tesar

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Guest Editor

1st Faculty of Medicine, General University Hospital, Department of Nephrology, Charles University, Prague, Czech Republic
Interests: glomerulonephritis; renal vasculitis; lupus nephritis; renal and renovascular hypertension; kidney amyloidosis; hereditary kidney disease; purification; hemodialysis; dialysis
Special Issues, Collections and Topics in MDPI journals

Dr. Andreas Kronbichler

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Guest Editor

Department of Internal Medicine IV (Nephrology and Hypertension), Anichstrasse 35, 6020 Innsbruck, Austria
Interests: vasculitis; nephrotic syndrome; glomerular disease; contrast-associated acute kidney injury; systemic lupus erythematosus
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Until recently, kidney disease was most frequently diagnosed exclusively based on histologic examination of kidney biopsy and treated with non-specific immunosuppression. The availability of new diagnostic methods resulted not only in a better understanding of the molecular pathogenesis of different kidney diseases and more specific and non-invasive diagnostics, but also in the identification of new molecular targets for more personalized treatment with putative better efficacy and safety. This Special Issue “Molecular Pathology, Diagnostics and Therapy of Kidney Disease” invites contributions of both original articles and reviews dedicated to the advanced diagnostics and new treatment approaches in chronic kidney disease. Attention is paid not only to glomerular disease, but also autosomal dominant polycystic kidney disease and kidney transplantation.

Prof. Dr. Vladimir Tesar
Dr. Andreas Kronbichler
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Related Special Issues

Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy 2.0 in International Journal of Molecular Sciences (13 articles)
Molecular Pathology, Diagnostics and Therapeutics of Nephropathy 3.0 in International Journal of Molecular Sciences (5 articles)

Published Papers (14 papers)

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Editorial

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4 pages, 199 KiB

Open AccessEditorial

Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy

by Andreas Kronbichler and Vladimir Tesar

Int. J. Mol. Sci. 2022, 23(24), 16006; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232416006 - 16 Dec 2022

Viewed by 1240

Abstract

Years of standing still have ended, and the field of nephrology has seen a plethora of clinical trials, changing the therapeutic landscape of chronic kidney disease (CKD) and immune-mediated kidney disease management [...] Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

Research

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12 pages, 1810 KiB

Open AccessArticle

Analysis of microRNAs in Small Urinary Extracellular Vesicles and Their Potential Roles in Pathogenesis of Renal ANCA-Associated Vasculitis

by Jana Frydlova, Iveta Zednikova, Veronika Satrapova, Eva Pazourkova, Sarka Santorova, Zdenka Hruskova, Vladimir Tesar, Martin Vokurka, Petr Prikryl and Marie Korabecna

Int. J. Mol. Sci. 2022, 23(8), 4344; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084344 - 14 Apr 2022

Cited by 4 | Viewed by 1878

Abstract

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) represents an autoimmunity disease characterized by high mortality. For successful treatment, the detailed knowledge of its complex pathogenesis and the set of biomarkers for differential diagnostics are desired. Analysis of molecular content of small urinary extracellular vesicles (uEV) offers the possibility to find markers in the form of microRNAs (miRNAs) and study the pathways involved in pathogenesis. We used next-generation sequencing in the first preliminary study to detect the miRNAs with altered expression in uEVs of patients with AAV in comparison with age-matched controls. We confirmed the results using single-target quantitative polymerase chain reaction tests on different sets of samples and found five miRNAs (miR-30a-5p, miR-31-3p, miR-99a-5p, miR-106b-5p, miR-182-5p) with highly elevated levels in uEVs of patients. We performed the comparison of their targets with the differentially expressed proteins in uEVs of patients included in the first phase. We realized that upregulated miRNAs and proteins in uEVs in AAV patients target different biological pathways. The only overlap was detected in pathways regulating the actin cytoskeleton assembly and thus potentially affecting the glomerular functions. The associations of upregulated miRNAs with pathways that were neglected as components of complex AAV pathogenesis, e.g., the epidermal growth factor receptor signaling pathway, were found. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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10 pages, 2050 KiB

Open AccessArticle

The Therapeutic Potential of Zinc-Alpha2-Glycoprotein (AZGP1) in Fibrotic Kidney Disease

by Inga Sörensen-Zender, Song Rong, Hermann Haller and Roland Schmitt

Int. J. Mol. Sci. 2022, 23(2), 646; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020646 - 07 Jan 2022

Cited by 3 | Viewed by 2023

Abstract

Chronic kidney disease (CKD) is characterized by a long-term loss of kidney function and, in most cases, by progressive fibrosis. Zinc-alpha2-glycoprotein (AZGP1) is a secreted protein, which is expressed in many different tissues and has been associated with a variety of functions. In a previous study, we have shown in cell culture and in AZGP1 deficient mice that AZGP1 has protective anti-fibrotic effects. In the present study, we tested the therapeutic potential of an experimental increase in AZGP1 using two different strategies. (1) C57Bl/6J mice were treated systemically with recombinant AZGP1, and (2) a transgenic mouse strain was generated to overexpress AZGP1 conditionally in proximal tubular cells. Mice underwent unilateral uretic obstruction as a pro-fibrotic kidney stress model, and kidneys were examined after 14 days. Recombinant AZGP1 treatment was accompanied by better preservation of tubular integrity, reduced collagen deposition, and lower expression of injury and fibrosis markers. Weaker but similar tendencies were observed in transgenic AZGP1 overexpressing mice. Higher AZGP1 levels led to a significant reduction in stress-induced accumulation of tubular lipid droplets, which was paralleled by improved expression of key players in lipid metabolism and fatty acid oxidation. Together these data show beneficial effects of elevated AZGP1 levels in fibrotic kidney disease and highlight a novel link to tubular cell lipid metabolism, which might open up new opportunities for CKD treatment. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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14 pages, 623 KiB

Open AccessCommunication

A Meta-Analysis of Human Transcriptomics Data in the Context of Peritoneal Dialysis Identifies Novel Receptor-Ligand Interactions as Potential Therapeutic Targets

by Michail Evgeniou, Juan Manuel Sacnun, Klaus Kratochwill and Paul Perco

Int. J. Mol. Sci. 2021, 22(24), 13277; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413277 - 10 Dec 2021

Cited by 3 | Viewed by 2392

Abstract

Peritoneal dialysis (PD) is one therapeutic option for patients with end-stage kidney disease (ESKD). Molecular profiling of samples from PD patients using different Omics technologies has led to the discovery of dysregulated molecular processes due to PD treatment in recent years. In particular, a number of transcriptomics (TX) datasets are currently available in the public domain in the context of PD. We set out to perform a meta-analysis of TX datasets to identify dysregulated receptor-ligand interactions in the context of PD-associated complications. We consolidated transcriptomics profiles from twelve untargeted genome-wide gene expression studies focusing on human cell cultures or samples from human PD patients. Gene set enrichment analysis was used to identify enriched biological processes. Receptor-ligand interactions were identified using data from CellPhoneDB. We identified 2591 unique differentially expressed genes in the twelve PD studies. Key enriched biological processes included angiogenesis, cell adhesion, extracellular matrix organization, and inflammatory response. We identified 70 receptor-ligand interaction pairs, with both interaction partners being dysregulated on the transcriptional level in one of the investigated tissues in the context of PD. Novel receptor-ligand interactions without prior annotation in the context of PD included BMPR2-GDF6, FZD4-WNT7B, ACKR2-CCL2, or the binding of EPGN and EREG to the EGFR, as well as the binding of SEMA6D to the receptors KDR and TYROBP. In summary, we have consolidated human transcriptomics datasets from twelve studies in the context of PD and identified sets of novel receptor-ligand pairs being dysregulated in the context of PD that warrant investigation in future functional studies. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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16 pages, 2101 KiB

Open AccessArticle

In Vivo Renin Activity Imaging in the Kidney of Progeroid Ercc1 Mutant Mice

by Bibi S. van Thiel, Janette van der Linden, Yanto Ridwan, Ingrid M. Garrelds, Marcel Vermeij, Marian C. Clahsen-van Groningen, Fatimunnisa Qadri, Natalia Alenina, Michael Bader, Anton J. M. Roks, A. H. Jan Danser, Jeroen Essers and Ingrid van der Pluijm

Int. J. Mol. Sci. 2021, 22(22), 12433; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212433 - 18 Nov 2021

Cited by 2 | Viewed by 2429

Abstract

Changes in the renin–angiotensin system, known for its critical role in the regulation of blood pressure and sodium homeostasis, may contribute to aging and age-related diseases. While the renin–angiotensin system is suppressed during aging, little is known about its regulation and activity within tissues. However, this knowledge is required to successively treat or prevent renal disease in the elderly. Ercc1 is involved in important DNA repair pathways, and when mutated causes accelerated aging phenotypes in humans and mice. In this study, we hypothesized that unrepaired DNA damage contributes to accelerated kidney failure. We tested the use of the renin-activatable near-infrared fluorescent probe ReninSense680™ in progeroid Ercc1^d/− mice and compared renin activity levels in vivo to wild-type mice. First, we validated the specificity of the probe by detecting increased intrarenal activity after losartan treatment and the virtual absence of fluorescence in renin knock-out mice. Second, age-related kidney pathology, tubular anisokaryosis, glomerulosclerosis and increased apoptosis were confirmed in the kidneys of 24-week-old Ercc1^d/− mice, while initial renal development was normal. Next, we examined the in vivo renin activity in these Ercc1^d/− mice. Interestingly, increased intrarenal renin activity was detected by ReninSense in Ercc1^d/− compared to WT mice, while their plasma renin concentrations were lower. Hence, this study demonstrates that intrarenal RAS activity does not necessarily run in parallel with circulating renin in the aging mouse. In addition, our study supports the use of this probe for longitudinal imaging of altered RAS signaling in aging. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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18 pages, 8406 KiB

Open AccessArticle

The Protective Role of Prolyl Oligopeptidase (POP) Inhibition in Kidney Injury Induced by Renal Ischemia–Reperfusion

by Giovanna Casili, Alessio Ardizzone, Rossella Basilotta, Marika Lanza, Alessia Filippone, Irene Paterniti, Emanuela Esposito and Michela Campolo

Int. J. Mol. Sci. 2021, 22(21), 11886; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111886 - 02 Nov 2021

Cited by 6 | Viewed by 2130

Abstract

Ischemia/reperfusion injury (IRI) is a complex pathophysiological process characterized by blood circulation disorder caused by various factors, such as traumatic shock, surgery, organ transplantation, and thrombus. Severe metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow to the ischemic tissue. The kidney is a highly perfused organ, sensitive to ischemia and reperfusion injury, and the incidence of renal IRI has high morbidity and mortality. Several studies showed that infiltration of inflammatory cells, apoptosis, and angiogenesis are important mechanisms involved in renal IRI. Despite advances in research, effective therapies for renal IRI are lacking. Recently it has been demonstrated the role of KYP2047, a selective inhibitor of prolyl oligopeptidase (POP), in the regulation of inflammation, apoptosis, and angiogenesis. Thus, this research focused on the role of POP in kidney ischemia/reperfusion (KI/R). An in vivo model of KI/R was performed and mice were subjected to KYP2047 treatment (intraperitoneal, 0.5, 1 and 5 mg/kg). Histological analysis, Masson’s trichrome and periodic acid shift (PAS) staining, immunohistochemical and Western blots analysis, real-time PCR (RT-PCR) and ELISA were performed on kidney samples. Moreover, serum creatinine and blood urea nitrogen (BUN) were quantified. POP-inhibition by KYP2047 treatment, only at the doses of 1 and 5 mg/kg, significantly reduced renal injury and collagen amount, regulated inflammation through canonical and non-canonical NF-κB pathway, and restored renal function. Moreover, KYP2047 modulated angiogenesis markers, such as TGF-β and VEGF, also slowing down apoptosis. Interestingly, treatment with KYP2047 modulated PP2A activity. Thus, these findings clarified the role of POP inhibition in AKI, also offering novel therapeutic target for renal injury after KI/R. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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19 pages, 13238 KiB

Open AccessArticle

Role of Human Primary Renal Fibroblast in TGF-β1-Mediated Fibrosis-Mimicking Devices

by Seong-Hye Hwang, Yun-Mi Lee, Yunyeong Choi, Hyung Eun Son, Ji Young Ryu, Ki Young Na, Ho Jun Chin, Noo Li Jeon and Sejoong Kim

Int. J. Mol. Sci. 2021, 22(19), 10758; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910758 - 05 Oct 2021

Cited by 6 | Viewed by 3070

Abstract

Renal fibrosis is a progressive chronic kidney disease that ultimately leads to end-stage renal failure. Despite several approaches to combat renal fibrosis, an experimental model to evaluate currently available drugs is not ideal. We developed fibrosis-mimicking models using three-dimensional (3D) co-culture devices designed with three separate layers of tubule interstitium, namely, epithelial, fibroblastic, and endothelial layers. We introduced human renal proximal tubular epithelial cells (HK-2), human umbilical-vein endothelial cells, and patient-derived renal fibroblasts, and evaluated the effects of transforming growth factor-β (TGF-β) and TGF-β inhibitor treatment on this renal fibrosis model. The expression of the fibrosis marker alpha smooth muscle actin upon TGF-β1 treatment was augmented in monolayer-cultured HK-2 cells in a 3D disease model. In the vascular compartment of renal fibrosis models, the density of vessels was increased and decreased in the TGF-β-treated group and TGF-β-inhibitor treatment group, respectively. Multiplex ELISA using supernatants in the TGF-β-stimulating 3D models showed that pro-inflammatory cytokine and growth factor levels including interleukin-1 beta, tumor necrosis factor alpha, basic fibroblast growth factor, and TGF-β1, TGF-β2, and TGF-β3 were increased, which mimicked the fibrotic microenvironments of human kidneys. This study may enable the construction of a human renal fibrosis-mimicking device model beyond traditional culture experiments. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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17 pages, 1500 KiB

Open AccessArticle

Exploratory Metabolomic Analysis Based on Reversed-Phase Liquid Chromatography–Mass Spectrometry to Study an In Vitro Model of Hypoxia-Induced Metabolic Alterations in HK-2 Cells

by Samuel Bernardo-Bermejo, Elena Sánchez-López, Lei Tan, Selma Benito-Martínez, Zhengjin Jiang, María Castro-Puyana, Francisco Javier Lucio-Cazaña and María Luisa Marina

Int. J. Mol. Sci. 2021, 22(14), 7399; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147399 - 09 Jul 2021

Cited by 3 | Viewed by 2047

Abstract

Oxygen deficiency in cells, tissues, and organs can not only prevent the proper development of biological functions but it can also lead to several diseases and disorders. In this sense, the kidney deserves special attention since hypoxia can be considered an important factor in the pathophysiology of both acute kidney injury and chronic kidney disease. To provide better knowledge to unveil the molecular mechanisms involved, new studies are necessary. In this sense, this work aims to study, for the first time, an in vitro model of hypoxia-induced metabolic alterations in human proximal tubular HK-2 cells because renal proximal tubules are particularly susceptible to hypoxia. Different groups of cells, cultivated under control and hypoxia conditions at 0.5, 5, 24, and 48 h, were investigated using untargeted metabolomic approaches based on reversed-phase liquid chromatography–mass spectrometry. Both intracellular and extracellular fluids were studied to obtain a large metabolite coverage. On the other hand, multivariate and univariate analyses were carried out to find the differences among the cell groups and to select the most relevant variables. The molecular features identified as affected metabolites were mainly amino acids and Amadori compounds. Insights about their biological relevance are also provided. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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13 pages, 1751 KiB

Open AccessArticle

Coregulation Analysis of Mechanistic Biomarkers in Autosomal Dominant Polycystic Kidney Disease

by Johannes Leierer, Paul Perco, Benedikt Hofer, Susanne Eder, Alexander Dzien, Julia Kerschbaum, Michael Rudnicki and Gert Mayer

Int. J. Mol. Sci. 2021, 22(13), 6885; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136885 - 26 Jun 2021

Cited by 6 | Viewed by 2148

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder leading to deterioration of kidney function and end stage kidney disease (ESKD). A number of molecular processes are dysregulated in ADPKD but the exact mechanism of disease progression is not fully understood. We measured protein biomarkers being linked to ADPKD-associated molecular processes via ELISA in urine and serum in a cohort of ADPKD patients as well as age, gender and eGFR matched CKD patients and healthy controls. ANOVA and t-tests were used to determine differences between cohorts. Spearman correlation coefficient analysis was performed to assess coregulation patterns of individual biomarkers and renal function. Urinary epidermal growth factor (EGF) and serum apelin (APLN) levels were significantly downregulated in ADPKD patients. Serum vascular endothelial growth factor alpha (VEGFA) and urinary angiotensinogen (AGT) were significantly upregulated in ADPKD patients as compared with healthy controls. Arginine vasopressin (AVP) was significantly upregulated in ADPKD patients as compared with CKD patients. Serum VEGFA and VIM concentrations were positively correlated and urinary EGF levels were negatively correlated with urinary AGT levels. Urinary EGF and AGT levels were furthermore significantly associated with estimated glomerular filtration rate (eGFR) in ADPKD patients. In summary, altered protein concentrations in body fluids of ADPKD patients were found for the mechanistic markers EGF, APLN, VEGFA, AGT, AVP, and VIM. In particular, the connection between EGF and AGT during progression of ADPKD warrants further investigation. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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Review

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New Insights into the Treatment of Glomerular Diseases: When Mechanisms Become Vivid

by Da-Wei Lin, Cheng-Chih Chang, Yung-Chien Hsu and Chun-Liang Lin

Int. J. Mol. Sci. 2022, 23(7), 3525; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073525 - 24 Mar 2022

Cited by 9 | Viewed by 4466

Abstract

Treatment for glomerular diseases has been extrapolated from the experience of other autoimmune disorders while the underlying pathogenic mechanisms were still not well understood. As the classification of glomerular diseases was based on patterns of juries instead of mechanisms, treatments were typically the art of try and error. With the advancement of molecular biology, the role of the immune agent in glomerular diseases is becoming more evident. The four-hit theory based on the discovery of gd-IgA1 gives a more transparent outline of the pathogenesis of IgA nephropathy (IgAN), and dysregulation of Treg plays a crucial role in the pathogenesis of minimal change disease (MCD). An epoch-making breakthrough is the discovery of PLA2R antibodies in the primary membranous nephropathy (pMN). This is the first biomarker applied for precision medicine in kidney disease. Understanding the immune system’s role in glomerular diseases allows the use of various immunosuppressants or other novel treatments, such as complement inhibitors, to treat glomerular diseases more reasonable. In this era of advocating personalized medicine, it is inevitable to develop precision medicine with mechanism-based novel biomarkers and novel therapies in kidney disease. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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17 pages, 683 KiB

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Autosomal Dominant Polycystic Kidney Disease: From Pathophysiology of Cystogenesis to Advances in the Treatment

by Jana Reiterová and Vladimír Tesař

Int. J. Mol. Sci. 2022, 23(6), 3317; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063317 - 19 Mar 2022

Cited by 14 | Viewed by 6541

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease, with an estimated prevalence between 1:1000 and 1:2500. It is mostly caused by mutations of the PKD1 and PKD2 genes encoding polycystin 1 (PC1) and polycystin 2 (PC2) that regulate cellular processes such as fluid transport, differentiation, proliferation, apoptosis and cell adhesion. Reduction of calcium ions and induction of cyclic adenosine monophosphate (sAMP) promote cyst enlargement by transepithelial fluid secretion and cell proliferation. Abnormal activation of MAPK/ERK pathway, dysregulated signaling of heterotrimeric G proteins, mTOR, phosphoinositide 3-kinase, AMPK, JAK/STAT activator of transcription and nuclear factor kB (NF-kB) are involved in cystogenesis. Another feature of cystic tissue is increased extracellular production and recruitment of inflammatory cells and abnormal connections among cells. Moreover, metabolic alterations in cystic cells including defective glucose metabolism, impaired beta-oxidation and abnormal mitochondrial activity were shown to be associated with cyst expansion. Although tolvaptan has been recently approved as a drug that slows ADPKD progression, some patients do not tolerate tolvaptan because of frequent aquaretic. The advances in the knowledge of multiple molecular pathways involved in cystogenesis led to the development of animal and cellular studies, followed by the development of several ongoing randomized controlled trials with promising drugs. Our review is aimed at pathophysiological mechanisms in cystogenesis in connection with the most promising drugs in animal and clinical studies. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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17 pages, 722 KiB

Open AccessReview

Sodium Glucose Cotransporter-2 Inhibitors: Spotlight on Favorable Effects on Clinical Outcomes beyond Diabetes

by Věra Čertíková Chábová and Oskar Zakiyanov

Int. J. Mol. Sci. 2022, 23(5), 2812; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052812 - 04 Mar 2022

Cited by 9 | Viewed by 3085

Abstract

Sodium glucose transporter type 2 (SGLT2) molecules are found in proximal tubules of the kidney, and perhaps in the brain or intestine, but rarely in any other tissue. However, their inhibitors, intended to improve diabetes compensation, have many more beneficial effects. They improve kidney and cardiovascular outcomes and decrease mortality. These benefits are not limited to diabetics but were also found in non-diabetic individuals. The pathophysiological pathways underlying the treatment success have been investigated in both clinical and experimental studies. There have been numerous excellent reviews, but these were mostly restricted to limited aspects of the knowledge. The aim of this review is to summarize the known experimental and clinical evidence of SGLT2 inhibitors’ effects on individual organs (kidney, heart, liver, etc.), as well as the systemic changes that lead to an improvement in clinical outcomes. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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14 pages, 1334 KiB

Open AccessReview

Vancomycin-Associated Acute Kidney Injury: A Narrative Review from Pathophysiology to Clinical Application

by Wei-Chih Kan, Yi-Chih Chen, Vin-Cent Wu and Chih-Chung Shiao

Int. J. Mol. Sci. 2022, 23(4), 2052; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23042052 - 12 Feb 2022

Cited by 27 | Viewed by 9545

Abstract

Vancomycin is the most frequently used antibiotic, accounting for up to 35% of hospitalized patients with infection, because of its optimal bactericidal effectiveness and relatively low price. Vancomycin-associated AKI (VA-AKI) is a clinically relevant but not yet clearly understood entity in critically ill patients. The current review comprehensively summarizes the pathophysiological mechanisms of, biomarkers for, preventive strategies for, and some crucial issues with VA-AKI. The pathological manifestations of VA-AKI include acute tubular necrosis, acute tubulointerstitial nephritis (ATIN), and intratubular crystal obstruction. The proposed pathological mechanisms of VA-AKI include oxidative stress and allergic reactions induced by vancomycin and vancomycin-associated tubular casts. Concomitant administration with other nephrotoxic antibiotics, such as piperacillin–tazobactam, high vancomycin doses, and intermittent infusion strategies compared to the continuous infusion are associated with a higher risk of VA-AKI. Several biomarkers could be applied to predict and diagnose VA-AKI. To date, no promising therapy is available. Oral steroids could be considered for patients with ATIN, whereas hemodialysis might be applied to remove vancomycin from the patient. In the future, disclosing more promising biomarkers that could precisely identify populations susceptible to VA-AKI and detect VA-AKI occurrence early on, and developing pharmacological agents that could prevent or treat VA-AKI, are the keys to improve the prognoses of patients with severe infection who probably need vancomycin therapy. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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21 pages, 2687 KiB

Open AccessReview

Kidney Damage Caused by Obesity and Its Feasible Treatment Drugs

by Meihui Wang, Zixu Wang, Yaoxing Chen and Yulan Dong

Int. J. Mol. Sci. 2022, 23(2), 747; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020747 - 11 Jan 2022

Cited by 34 | Viewed by 8098

Abstract

The rapid growth of obesity worldwide has made it a major health problem, while the dramatic increase in the prevalence of obesity has had a significant impact on the magnitude of chronic kidney disease (CKD), especially in developing countries. A vast amount of researchers have reported a strong relationship between obesity and chronic kidney disease, and obesity can serve as an independent risk factor for kidney disease. The histological changes of kidneys in obesity-induced renal injury include glomerular or tubular hypertrophy, focal segmental glomerulosclerosis or bulbous sclerosis. Furthermore, inflammation, renal hemodynamic changes, insulin resistance and lipid metabolism disorders are all involved in the development and progression of obesity-induced nephropathy. However, there is no targeted treatment for obesity-related kidney disease. In this review, RAS inhibitors, SGLT2 inhibitors and melatonin would be presented to treat obesity-induced kidney injury. Furthermore, we concluded that melatonin can protect the kidney damage caused by obesity by inhibiting inflammation and oxidative stress, revealing its therapeutic potential. Full article

(This article belongs to the Special Issue Molecular Pathology, Diagnostics, and Therapeutics of Nephropathy)

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